Compositions for treating acne comprising phytandiol amine

ABSTRACT

The present invention relates to a phytandiol amine derivative represented by the following formula (I) and compositions for treating acne comprising the same: 
     
       
         
         
             
             
         
       
         
         
           
             wherein each of Y and Z is OH with the proviso that X is NH 2 , each of X and Z is zOH with the proviso that Y is NH 2 , and each of X and Y is OH with the proviso that Z is NH 2 .

This application is the US national phase of international applicationPCT/KR01/01838, filed 31 Oct. 2001, which designated the US.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to novel phytandiol amine derivatives andtheir use for treatment or prevention of acne. More particularly, thepresent invention relates to novel phytandiol amine derivatives andcompositions for improving or alleviating acne comprising the abovederivatives as active ingredient.

2. Description of the Related Art

Acne is inflammatory disease or disorder generally developed at sebumgland in hair follicle of skin, of which etiopathology, althoughunclear, is suggested as follows: Excess secretion of sebum triggered bytestosterone, one of androgenic hormones, contributes todyskeratinization of pilosebaceous canal, and in turn results inblockage in orifice for secretion of sebum, thereby accumulation ofsebum in hair follicle. Excess accumulation of sebum is responsible forovergrowth of acne-causing bacteria, e.g. Propionibacterium acnes, insuch follicle, and the lipase secreted from the bacteria hydrolyzes theaccumulated sebum to form free fatty acids giving rise to inflammationthrough irritation of skin. Also, acne-causing bacteria, recognized asantigen, elicit immune reaction of individuals, resulting ininflammatory reaction. In accordance with such mechanism, papule andinflammatory acne are developed, and when aggravated, wall of thefollicle is disrupted and sequentially tissues are injured, finallyleading to lesions of vesicular and pustule.

In an effort to inhibit generation and development of acne, a variety ofpharmaceuticals formulated in the form of oral-administered drug orexternal preparation have been developed and employed. Suchpharmaceuticals are: (a) anti-androgen agent for regulating secretion ofandrogenic hormones; (b) non-steroidal antiphlogostic agent exhibitingantinflammtory function; and (c) antimicrobial agents such asresorcinol, benzoyl peroxide, erythromycin and tetracycline to inhibit agrowth of acne-causing bacteria. Recently, it is commonly employed totreat acne using retinoic acid and vitamin A derivatives.

Most of therapeutics for acne, however, is unfortunately suffered fromadverse effects including inhibition of growth of epiderm, irritation ordyskeratinization of skin, resistance to antimicrobial agents andapplicability.

Therefore, the use of low-irritating antimicrobial extracted fromseveral plants has been recently attempted for controlling acne-causingbacteria in the field of cosmetics. Unfortunately, recent attempts asabove-mentioned have recognized some drawbacks: (a) low antimicrobialactivity and (b) inefficiency of separation and purification of activeingredient from natural sources.

Under such circumstances, many researches have continuously focused onsubstances or compositions for treating acne disease or disorder withboth better compatibility to human body and greater efficacy.

U.S. Pat. No. 6,168,798 discloses non-irritating compositions fortreating acne and other skin conditions comprising salicylic acid asactive ingredient, and U.S. Pat. No. 6,174,892 discloses a method oftreating acne with 5-alpha reductase inhibitors such as finasteride.

In addition, U.S. Pat. No. 4,775,663 suggests compositions for treatingacne containing benzofuran derivatives and U.S. Pat. No. 5,019,567discloses benzoyl peroxide-quaternary ammonium lipophilic salicylatebased pharmaceutical and cosmetic compositions and their use especiallyin treatment of acne.

Throughout this application, various patents are reference and citationsare provided in parentheses. The disclosure of these patents in theirentities are hereby incorporated by references into this application inorder to more fully describe this invention and the state of the art towhich this invention pertains.

SUMMARY OF THE INVENTION

In one aspect of this invention, there is provided a phytandiol aminederivative represented by the following formula (I):

wherein each of Y and Z is OH with the proviso that X is NH₂, each of Xand Z is OH with the proviso that Y is NH₂, and each of X and Y is OHwith the proviso that Z is NH₂.

In another aspect of this invention, there is provided a cosmeticcomposition for improving or alleviating acne, which comprises: (a) acosmetically effective amount of phytandiol amine derivatives as activeingredient represented by the following formula (I); and (b) acosmetically acceptable carrier,

wherein each of Y and Z is OH with the proviso that X is NH₂, each of Xand Z is OH with the proviso that Y is NH₂, and each of X and Y is OHwith the proviso that Z is NH₂.

In still another aspect of this invention, there is provided apharmaceutical composition for treating or preventing acne, whichcomprises: (a) a pharmaceutically effective amount of phytandiol aminederivatives as active ingredient represented by the following formula(I); and

-   -   (b) a pharmaceutically acceptable carrier,

wherein each of Y and Z is OH with the proviso that X is NH₂, each of Xand Z is OH with the proviso that Y is NH₂, and each of X and Y is OHwith the proviso that Z is NH₂.

Accordingly, it is an object of this invention to provide novelphytandiol amine derivatives.

It is another object of this invention to provide a cosmetic compositionfor improving or alleviating acne comprising the above derivatives asactive ingredient.

It is still another object of this invention to provide a pharmaceuticalcomposition for treating or preventing acne comprising the abovederivatives as active ingredient.

Other objects and advantages of the present invention will becomeapparent from the detailed description to follow taken in conjugationwith the appended claims.

DETAILED DESCRIPTION OF THIS INVENTION

The present invention is primarily directed to novel phytandiol aminederivatives. The derivatives have been prepared during the developmentof novel compounds highly effective in treating, alleviating orpreventing certain skin disorders or diseases, generally called acne.

The phytandiol amine derivatives of this invention may be prepared fromstarting materials such as phytantriol and phytol, which is commerciallyavailable.

As known in formula (I), the phytandiol amine derivatives of thisinvention have amphiphilic property, thereby contributing to a goodsolubility in both aqueous solvent and non-aqueous solvent, as well assurface-activating property, and further exhibit high stability at hightemperature, e.g., 90° C.–100° C., and at a very wide range of pH. Theabove-described properties are responsible for a high workability in theformulation of cosmetic or pharmaceutical composition, especially,composition for topical application.

The phytandiol amine derivatives of this invention may be classifiedinto three classes. The terms, “phytandiol amine derivative (I)” or“phytandiol amine (I)”, used herein, refer to a derivative of formula(I) in which each of Y and Z is OH with the proviso that X is NH₂.“Phytandiol amine derivative (II)” or “phytandiol amine (II)”, as theterms are used herein, refer to a derivative of formula (I) in whicheach of X and Z is OH with the proviso that Y is NH₂. The terms,“phytandiol amine derivative (III)” or “phytandiol amine (III)”, usedherein, refer to a derivative of formula (I) in which each of X and Y isOH with the proviso that Z is NH₂.

In the compositions of the present invention, the compounds representedby formula (I) employed as active ingredient, are very useful fortreating, alleviating and preventing acne, and exhibit an anti-acneefficacy through the inhibition of growth of acne-causing pathogens likePropionibacterium acnes and Propionibacterium avidum. The compounds offormula (I) show very low Minimum Inhibitory Concentration (hereinafterreferred to as “MIC”) against acne-causing pathogens.

The term “acne”, used herein, to which the present compositions areapplied, includes all skin diseases or disorders generally called acneas well as all skin diseases or disorders which have a similar pathologyto one of acne. For examples, the acne includes, but not limited to,acne aggregate, bromide acne, common acne, congoblate acne, acnecosmetics, acne dtergicans, acne ephebica, acne fulminans, acnefurunculoid, halogen acne, acne indurate, acne keloid, mechanical acne,acne medicamentosa, acne necrotica miliaris, acne neonatorum, acne oil,acne papulosa, pomade acne, premenstrual acne, acne rosacea, acnesycosiformis, tropical acne, acne venenata, and acne vulgaris.

In the compositions of this invention, the amount of phytadiol aminederivatives is preferably in the range of 0.001–50 wt %, morepreferably, 0.01–20 wt % and the most preferably, 0.05–5 wt %.

The cosmetic compositions of this invention may be formulated in a widevariety of form, for example, including a solution, a suspension, anemulsion, a paste, an ointment, a gel, a cream, a lotion, a powder, asoap, a surfactant-containing cleanser, an oil, a powder foundation, anemulsion foundation, a wax foundation and a spray.

The cosmetically acceptable carrier contained in the present cosmeticcomposition, may be varied depending on the type of the formulation. Forexample, the formulation of ointment, pastes, creams or gels maycomprise animal and vegetable fats, waxes, paraffins, starch,tragacanth, cellulose derivatives, polyethylene glycols, silicones,bentonites, silica, talc, zinc oxide or mixtures of these substances. Inthe formulation of powder or spray, it may comprise lactose, talc,silica, aluminum hydroxide, calcium silicate, polyamide powder andmixtures of these substances. Spray may additionally comprise thecustomary propellants, for example, chlorofluorohydrocarbons,propane/butane or dimethyl ether.

The formulation of solution and emulsion may comprise solvent,solubilizer and emulsifier, for example water, ethanol, isopropanol,ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate,propylene glycol, 1,3-butylglycol, oils, in particular cottonseed oil,groundnut oil, maize germ oil, olive oil, castor oil and sesame seedoil, glycerol fatty esters, polyethylene glycol and fatty acid esters ofsorbitan or mixtures of these substances. The formulation of suspensionmay comprise liquid diluents, for example water, ethanol or propyleneglycol, suspending agents, for example ethoxylated isosteary alcohols,polyoxyethylene sorbitol esters and poly oxyethylene sorbitan esters,micocrystalline cellulose, aluminum metahydroxide, bentonite, agar andtragacanth or mixtures of these substances.

The formulation of soap may comprise alkali metal salts of fatty acids,salts of fatty acid hemiesters, fatty acid protein hydrolyzates,isethionates, lanolin, fatty alcohol, vegetable oil, glycerol, sugars ormixtures of these substances.

Furthermore, the cosmetic compositions of this invention, may containauxiliaries as well as carrier. The non-limiting examples of auxiliariesinclude preservatives, antioxidants, stabilizers, solubilizers,vitamins, colorants, odor improvers or mixtures of these substances

In the pharmaceutical compositions of this invention, thepharmaceutically acceptable carrier may be conventional one forformulation, including lactose, dextrose, sucrose, sorbitol, mannitol,starch, gum acacia, calcium phosphate, alginate, gelatin, calciumsilicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose,water, syrup, methyl cellulose, methylhydroxy benzoate, propylhydroxybenzoate, talc, stearic acid, magnesium and mineral oil, but not limitedto. The pharmaceutical compositions of this invention, further maycontain wetting agent, sweetening agent, emulsifying agent, suspendingagent, preservatives, flavors, perfumes, lubricating agent, or mixturesof these substances.

The pharmaceutical compositions of this invention, may be administeredorally or parenterally. The topical administration, especially topicalapplication to skin, is the most preferable mode for the presentcompositions.

The correct dosage of the pharmaceutical compositions of this inventionwill vary according to the particular formulation, the mode ofapplication, age, body weight and sex of the patient, diet, time ofadministration, condition of the patient, drug combinations, reactionsensitivities and severity of the disease. It is understood that theordinary skilled physician will readily be able to determine andprescribe a correct dosage of this pharmaceutical compositions. Anexemplary daily dosage unit for human host comprises an amount of fromabout 0.001 mg/kg to about 100 mg/kg.

According to the conventional techniques known to those skilled in theart, the pharmaceutical compositions of this invention can be formulatedwith pharmaceutical acceptable carrier and/or vehicle as describedabove, finally providing several forms including a unit dosage form.Non-limiting examples of the formulations include, but not limited to, asolution, a suspension or an emulsion, an extract, an elixir, a powder,a granule, a tablet, a capsule, emplastra, a liniment, a lotion and anointment.

The compositions of this invention are significantly effective intreating, alleviating and preventing acne without irritation andkeratinization of skin and induction of resistance to antimicrobialagents even the case of a long-term application.

The following specific examples are intended to be illustrative of theinvention and should not be construed as limiting the scope of theinvention as defined by appended claims.

EXAMPLE Example I Preparation of Phytandiol Amine Derivative [I]

In a reactor 0.3 g of phytantriol (0.91 mmol) was dissolved in 20 ml ofnormal hexane and stirred for 10 min. at a room temperature, followed byaddition of 0.21 g (1.09 mmol) of para-toluene sulfonylchloride.Following the drop of the temperature of the reactor to 0° C., 0.11 g(1.09 mmol) of triethyl amine and a catalytic amount of pyridine wereadded dropwise and the temperature of the reactor was elevated to a roomtemperature, followed by stirring for 12 hr. Upon the completion of thereaction, the solvent was removed by distillation under reducedpressure. Then, 20 ml of chloroform was added to the concentrate forextraction and the extract was washed with saline. The washed extractwas dried over anhydrous magnesium sulfate, followed by filtration andconcentration to yield 0.48 g para-toluene sulfonyl phytandiolderivative as brown oil.

The yielded phytandiol derivative (0.48 g) was dissolved in 25 ml ofdimethyl formamide and 0.06 g (1.00 mmol) of sodium azide was added,followed by reflux for 5 hr in order to substitute azide forpara-toluene sulfonyl group. The reaction mixture was extracted with 50ml of methylene chloride solution and washed with saline. Followingdrying over anhydrous magnesium sulfate, filtration and concentration,0.29 g of azido phytandiol derivative was yielded.

In order to convert the azido phytandiol derivative to amine compound,0.29 g of the yielded azido phytandiol (8.4 mmol) was subject tohydrogenation in ethyl alcohol with a catalytic amount of 10% palladiumcharcoal under 50 psi of hydrogen atmosphere for 3–4 hr, and finally0.21 g of phytandiol amine derivative [I] (0.64 mmol) was obtained inthe form of yellow gel in the overall yield of 70%: Anal. Calcd. forC₂₀H₄₃NO₂(329.33): C, 72,89; H, 13,15; N, 4,25; O, 9,71; Found C, 72,44;H, 13,51; N, 4,65; O, 9,98

Example II Preparation of Phytandiol Amine Derivative [II]

In a reactor 0.3 g of phytol (1.0 mmol) was dissolved in 30 ml ofmethylene chloride and then the temperature of the reactor was decreasedto 0° C. While maintaining the temperature of the reactor, to themixture was added 0.45 g of 77% chloroperoxy benzoic acid. After thecompletion of the reaction, the resultant was extracted with 50 ml ofchloroform to prepare phytol derivative epoxidated at 2- and3-positions. The phytol derivative was reacted with ammonia gas for 5hr. to produce 0.21 g of phytandiol amine derivative [II] in the yieldof 64%: Anal. Calcd. for C₂₀H₄₃NO₂(329.33): C, 72,89; H, 13,15; N, 4,25;O, 9,71; Found C, 72,44; H, 13,51; N, 4,65; O, 9.98

Example III Preparation of Phytandiol Amine Derivative [III]

One g of phytantriol (3.0 mmol) was refluxed using deanstock apparatusfor 15 hr in 25 ml of acetone solution with toluene sulfonic acid ascatalyst. After the completion of the reaction, the acetone solvent wasremoved under reduced pressure and the resultant was extracted withchloroform solution. The extract was washed with saturated sodiumbicarbonate solution and was again washed with saline to obtain 0.3 g of(2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-6,10,14-trimethyl-pentadecan-2-ol)of which 1- and 2-positions were protected, which is represented by thefollowing formula (IV):

Thereafter, in 20 ml of normal hexane was dissolved 0.3 g of(2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-6,10,14-trimethyl-pentadecan-2-ol),and stirred for 10 min. at a room temperature, followed by addition of0.18 g (0.97 mmol) of para-toluene sulfonylchloride. After the drop ofthe temperature of the reactor to 0° C., 3 equivalents of pyridine wereadded and the temperature of the reactor was elevated to a roomtemperature, followed by stirring for 12 hr. Upon the completion of thereaction, the solvent was removed by distillation under reducedpressure. Then, 20 ml of chloroform was added to the concentrate forextraction and the extract was washed with saline. The washed extractwas dried over anhydrous magnesium sulfate, followed by filtration andconcentration to yield 0.41 g of a compound substituted at 3-positionwith toluene sulfonyl in the form of yellow oil. In 20 ml of 2N HCl wasdissolved 0.41 g of the yellow oil, and then was reacted for 6 hr at 80°C. to yield 0.21 g of 1,2-phytandiol derivative of which ring structureis cleaved.

The phytandiol derivative yielded (0.21 g) was dissolved in 25 ml ofdimethyl formamide and 0.06 g (1.00 mmol) of sodium azide was added,followed by reflux for 5 hr to produce 0.15 g of phytandiol derivativesubstituted with azide. In order to reduce the azide-substitutedphytandiol derivative to amine compound, 0.15 g of the azido phytandiolyielded was subject to hydrogenation in ethyl alcohol with a catalyticamount of 10% palladium charcoal under 50 psi of hydrogen atmosphere for3–4 hr, and finally 0.20 g of phytandiol amine derivative [III] wasobtained in the yield of 50%: Anal. Calcd. for C₂₀H₄₃NO₂(329.33): C,72,89; H, 13,15; N, 4,25; O, 9,71; Found C, 72,51; H, 13,04; N, 4,54; O,9,43

Example IV Evaluation on Minimum Inhibitory Concentration

To evaluate an antimicrobial activity of the phytandiol amine of thisinvention against acne pathogen, the minimum inhibitory concentration(hereinafter referred to as “MIC”) of the samples shown in Table 1 wasmeasured as follows:

The sample to be tested was added to reinforced clostridial agar medium(available from Difco Co.) in the amount of 0.001–0.1%, followed bysolidification of the medium. The suspension of acne pathogenic bacteriafound in Table 1 was streaked on the surface of the medium and themedium was incubated for 3 days at 35° C. under anaerobic condition. TheMIC was measured by the determination of the minimum concentration tocompletely inhibit the growth of the acne pathogenic bacteria, of whichresults are indicated in Table 1.

TABLE 1 P. acnes P. acne P. avidum Sample/Pathogen ATCC 6919 ATCC 11828ATCC 25577 Phytandiol amine [I] 0.002 0.002 0.002 Phytandiol amine [II]0.002 0.002 0.002 Phytandiol amine [III] 0.003 0.004 0.003 Tea tree oil1.0 0.2 1.0 Erythromycin 0.02 0.02 0.02 Chitosan 0.2 0.2 0.2 Benzoylperoxide 0.1 0.1 0.1

As demonstrated in Table 1, the phytandiol amine derivatives of thisinvention represent antimicrobial activity against acne pathogens 10–50times greater than erythromycin and benzoyl peroxide which areconventionally used as a therapeutic agent for acne.

Furthermore, the phytandiol amine derivatives of this invention areimproved in terms of workability and skin-compatibility, thereby leadingto little adverse effects. Therefore, the phytandiol amine derivativesof this invention can be excellent agents for treating acne and thecompositions comprising the same are also expected to exhibit aremarkable treatment effect to acne.

Example V Evaluation on Antimicrobial Activity Against Acne Pathogen ofthe Formulation Comprising the Present Compounds

To elucidate antimicrobial activity against acne pathogens of thecompositions comprising the phytandiol amine derivatives of thisinvention, a particular formulation of skin lotion as externalapplication was prepared as the following Table 2. In Table 2, theamount of constituents is expressed in terms of wt %.

TABLE 2 Comp. Ingredients Prep. 1 Prep. 2 Exam. Phytandiol amine [I]0.05 0.1 — Glycerine 5.0 5.0 5.0 1,3-butylene glycol 3.0 3.0 3.0PEG-1500 1.0 1.0 1.0 DL-panthenol 0.3 0.3 0.3 EDTA 0.02 0.02 0.02Benzophenone-9 0.04 0.04 0.04 Sodium hyaluronate 5.0 5.0 5.0 Ethanol10.0 10.0 10.0 Octyldodeces-16 0.2 0.2 0.2 Polysorbate 20 0.2 0.2 0.2Allantoin 0.1 0.1 0.1 Preservative, Minute minute minute perfume,colorant amount amount amount Distilled water Residual Residual residualTotal 100 100 100

The antimicrobial activities against acne-causing bacteria of the skinlotions of preparative examples 1 and 2, and comparative example weremeasured as follows: The acne-causing bacteria were cultured at 35° C.under anaerobic condition, the colonies formed were taken with aplatinum loop and were appropriately diluted by suspending inphosphate-buffered saline. 10 ml of reinforced clostridial agar mediumwere poured into each of plates and solidified, and then the dilutedsolution containing acne-causing bacteria was inoculated into each ofthe plates to the extent of 300–500 cfu. The plates were cultured in ananaerobic incubator and the number of colonies formed was counted, whichis considered as the number of the original acne-causing bacteria(N_(ori)).

The skin lotions of preparative examples 1 and 2, and comparativeexample were respectively mixed with reinforced clostridial agar mediumto the extent of 10%, the acne-causing bacteria was inoculated into themixture and cultured as above. The number of colonies formed isconsidered as the number of the final acne-causing bacteria (N_(fin)).The antimicrobial activity against acne-causing bacteria was calculatedin accordance with following equation, which is indicated in Table 3.

EquationAntimicrobial Activity(%)=[(N_(ori)−N_(fin))/N_(ori)]×100

More than 90% of antimicrobial activity is evaluated as the possessionof antimicrobial activity against acne-causing bacteria.

TABLE 3 Comp. Items Prep. 1 Prep. 2 Exam. No. of original acne- 510 475380 causing bacteria (N_(ori)) No. of final acne- 31 2 219 causingbacteria (N_(fin)) Antimicrobial activity 93.9 99.5 42.3 againstacne-causing bacteria (%) Evaluation adequate adequate inadequate

As found in Table 3, the formulations comprising the phytandiol aminederivative [I] of this invention exhibit antimicrobial activity againstacne-causing bacteria much greater than the formulation without thederivative. In particular, the formulation containing 0.1 wt % ofphytandiol amine derivative [I] approaches to 100% of antimicrobialactivity.

While not shown in this specification, the formulations containing thephytandiol amine derivatives [II] or [III] of this invention give almostthe same antimicrobial activity as one containing the phytandiol aminederivative [I]

Consequently, it is sure that the compositions comprising the phytandiolamine derivatives of this invention are highly effective in treating orpreventing acne.

Example VI Evaluation on Improving or Alleviating Acne

First, 60 women aged 17–29 years, who had acne symptom on their face,were randomly divided to three groups. The formulations of preparativeexamples 1 or 2, or comparative example were topically applied twice aday to three groups, respectively, for six weeks, in the morning andevening. The improving or alleviating effect for acne was assessed withthe opinion from the tested women, which is indicated in Table 4.

TABLE 4 Time Period Prep. 1 Prep. 2 Com. Exam. 1 week ± ± ± 2 weeks + +± 3 weeks + ++ ± 4 weeks ++ +++ ± 5 weeks +++ +++ ± 6 weeks +++ +++ ±Note. +++: showing excellent improvement efficacy ++: showingsignificant improvement efficacy +: showing slight improvement efficacy±: not showing improvement efficacy but not showing aggravation efficacy−: showing aggravation efficacy

As demonstrated in Table 4, the formulations of skin lotion containingphytandiol amine derivative [I] of this invention exhibit excellentimprovement or alleviation effect on acne symptom, which appearsexplicitly from about 3 weeks after application. Furthermore, thecomposition of this invention did not lead to irritation of skin,erythema and itch.

Formulation Example

The following exemplified compositions were formulated according toconventional methods, which comprise the phytandiol amine [I] of thisinvention as active ingredient while the formulated compositions can bealso applied to other phytandiol amine derivatives of this invention.Therefore, those skilled in the art will promptly recognize appropriatevariations from the formulations both as to ingredients and as to theamount thereof.

Formulation I

Formulation I comprising the phytandiol amine [I] was prepared in theform of astringent cosmetic liquid, of which composition is found inTable 5.

TABLE 5 Ingredients Amount (wt %) Phytandiol amine [I] 0.1 Glycerine 2.01,3-butylene glycol 2.0 Allantoin 0.2 DL-panthenol 0.2 EDTA 0.02Benzophenone-9 0.04 Sodium hyaluronate 3.0 Ethanol 15.0 Polysorbate 200.3 Preservative, perfume, Minute quantity colorant Distilled waterResidual quantityFormulation II

Formulation II comprising the phytandiol amine [I] was prepared in theform of nutrient cosmetic liquid, of which composition is found in Table6.

TABLE 6 Ingredients Amount (wt %) Phytandiol amine [I] 0.1 Glycerylstearate 1.5 Stearyl alcohol 1.5 Lanoline 1.5 Polysorbate 1.3 Hardenedplant oil 1.0 Mineral oil 5.0 Squalane 3.0 Trioctanoine 2.0 Dimethicone0.8 Tocopheryl acetate 0.5 Carboxyvinyl polymer 0.12 Glycerine 5.01,3-butylene glycol 3.0 Sodium hyaluronate 5.0 Triethanol amine 0.12preservative, perfume, Minute quantity colorant Distilled water ResidualquantityFormulation III

Formulation III comprising the phytandiol amine [I] was prepared in theform of nutrient cream, of which composition is found in Table 7.

TABLE 7 Ingredients Amount (wt %) Phytandiol amine [I] 0.1 Lipophilicmonostearyl 2.0 glycerine Stearyl alcohol 2.2 Stearic acid 1.5 Wax 1.0Polysorbate 60 1.5 Sorbitan stearate 0.6 Hardened plant oil 1.0 Squalane3.0 Mineral oil 5.0 Trioctanoine 5.0 Dimethicone 1.0 Sodium magnesiumsilicate 0.1 Glycerine 5.0 Betaine 3.0 Triethanol amine 1.0 Sodiumhyaluronate 4.0 Preservative, perfume, Minute quantity colorantDistilled water Residual quantityFormulation IV

Formulation IV comprising the phytandiol amine [I] was prepared in theform of massage cream, of which composition is found in Table 8.

TABLE 8 Ingredients Amount (wt %) Phytandiol amine [I] 0.1 Lipophilicmonostearyl 1.5 glycerine Stearyl alcohol 1.5 Stearic acid 1.0Polysorbate 60 1.5 Sorbitan stearate 0.6 Isostearylisostearate 5.0Squalane 5.0 Mineral oil 35.0 Dimethicone 0.5 Hydroxyethyl cellulose0.12 Glycerine 6.0 Triethanol amine 0.7 Preservative, perfume, Minuteamount colorant Distilled water Residual amountFormulation V

Formulation V comprising the phytandiol amine [I] was prepared in theform of essence, of which composition is found in Table 9.

TABLE 9 Ingredients Amount (wt %) Phytandiol amine [I] 0.1 Glycerine10.0 Betaine 5.0 PEG-1500 2.0 Allantoin 0.1 DL-panthenol 0.3 EDTA 0.02Benzophenone-9 0.04 Hydroxyethylcellulose 0.1 Sodium hyaluronate 8.0Carboxyvinyl polymer 0.2 Triethanol amine 0.18 Octyldodeces-16 0.4Octyldodecanol 0.3 Ethanol 6.0 preservative, perfume, Minute amountcolorant Distilled water Residual amountFormulation VI

Formulation VI comprising the phytandiol amine [I] was prepared in theform of facial pack, of which composition is found in Table 10.

TABLE 10 Ingredients Amount (wt %) Phytandiol amine [I] 1.0 Polyvinylalcohol 15.0 Cellulose gum 0.15 Glycerine 3.0 PEG-1500 2.0 Cyclodextrine0.15 DL-panthenol 0.4 Allantoin 0.1 Glyceryl ammonium 0.3 Nicotine amide0.5 Ethanol 6.0 PEG-40 hardened castor oil 0.3 Preservative, perfume,Minute amount colorant Distilled water Residual amountFormulation VII

Formulation VII comprising the phytandiol amine [I] was prepared in theform of soap, of which composition is found in Table 11.

TABLE 11 Ingredients Amount (wt %) Palm oil fatty acid 1.5 Titania 0.5Glycerine 0.5 EDTA-2Na 0.15 Perfume 0.7 Phytandiol amine [I] 0.5Colorant Adequate quantity Soap chip base To 100 (water content, 15 wt%)

Having described a preferred embodiment of the present invention, it isto be understood that variants and modifications thereof falling withinthe spirit of the invention may become apparent to those skilled in thisart, and the scope of this invention is to be determined by appendedclaims and their equivalents.

1. A cosmetic composition for improving or alleviating acne, whichcomprises: (a) a cosmetically effective amount of phytandiol aminederivative as active ingredient represented by the following formula(I); and (b) a cosmetically acceptable carrier,

wherein each of Y and Z is OH with the proviso that X is NH₂, each of Xand Z is OH with the proviso that Y is NH₂, and each of X and Y is OHwith the proviso that Z is NH₂.
 2. The composition according to claim 1,wherein the acne is selected from the group consisting of acneaggregata, bromide acne, common acne, congoblate acne, acne cosmetica,acne dtergicans, acne ephebica, acne fulminans, acne furunculoid,halogen acne, acne indurate, acne keloid, mechanical acne, acnemedicamentosa, acne necrotica miliaris, acne neonatorum, acne oil, acnepapulosa, pomade acne, premenstrual acne, acne rosacea, acnesycosiformis, tropical acne, acne venenata and acne vulgaris.
 3. Thecomposition according to claim 1, wherein the phytandiol aminederivative is present in an amount of 0.01–20 wt % based on the totalweight of the composition.
 4. The composition according to claim 1,wherein the cosmetic composition is in the form of one selected from thegroup consisting of a solution, a suspension, an emulsion, a paste, anointment, a gel, a cream, a lotion, a powder, a soap, asurfactant-containing cleanser, an oil, a powder foundation, an emulsionfoundation, a wax foundation and a spray.